Interruption of tuberculosis detection and care during the Ebola virus disease epidemic (2014–2015) in Liberia: time-series analyses for 2013–2017

Objective Interrupted time-series analyses, using 5 years of routinely collected health information system data, were conducted to estimate the magnitude of impact of the 2014–2015 Ebola virus disease (EVD) epidemic and determine trends in tuberculosis (TB) care services in Liberia. Methods A segmented linear regression model was used to generate estimates and predictions for trends for three TB service indicators before, during, and after EVD, from January 2013 to December 2017. Results It was found that the number of presumptive TB cases declined significantly at the start of the EVD outbreak, with an estimated loss of 3222 cases (95% confidence interval (CI) −5691 to −752; P = 0.014). There was also an estimated loss of 709 cases per quarter post-EVD (95% CI −1346 to −71; P = 0.032). However, over the post-EVD period, quarterly increases were observed in the proportion of smear-positive to presumptive cases (1.45%, 95% CI 0.38% to 2.5%; P = 0.011) and the proportion of treatment success to TB cases evaluated (3.3%, 95% CI 0.82% to 5.79%; P = 0.013). Conclusions These findings suggest that the EVD outbreak (2014–2015) negatively affected TB care services. Rigorous quantitative analyses can be used to assess the magnitude of interruption and advocate for preparedness in settings with limited healthcare capacity

BioTIME: A database of biodiversity time series for the Anthropocene.

MotivationThe BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables includedThe database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grainBioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).Time period and grainBioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurementBioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.Software format.csv and .SQL

Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study

Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients’ experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants’ reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research

Complete genome sequence of Sebaldella termitidis type strain (NCTC 11300T)

Sebaldella termitidis (Sebald 1962) Collins and Shah 1986, is the only species in the genus Sebaldella within the fusobacterial family ‘Leptotrichiaceae’. The sole and type strain of the species was first isolated about 50 years ago from intestinal content of Mediterranean termites. The species is of interest for its very isolated phylogenetic position within the phylum Fusobacteria in the tree of life, with no other species sharing more than 90% 16S rRNA sequence similarity. The 4,486,650 bp long genome with its 4,210 protein-coding and 54 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project

Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016–2019

Background Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The “Treat all” strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 –December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30–45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8–51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21–2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51–3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35–44 (aHR 0.65, 95%CI: 0.44–0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39–0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53–3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75–3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57–6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51–0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20–0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects–average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06–1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11–2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01–0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004–0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes

Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016–2019

Background Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The “Treat all” strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 –December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30–45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8–51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21–2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51–3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35–44 (aHR 0.65, 95%CI: 0.44–0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39–0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53–3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75–3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57–6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51–0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20–0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects–average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06–1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11–2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01–0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004–0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes

Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia

NUP98 fusions comprise a family of rare recurrent alterations in AML, associated with adverse outcomes. In order to define the underlying biology and clinical implications of this family of fusions, we performed comprehensive transcriptome, epigenome, and immunophenotypic profiling of 2,235 children and young adults with AML and identified 160 NUP98 rearrangements (7.2%), including 108 NUP98-NSD1 (4.8%), 32 NUP98-KDM5A (1.4%) and 20 NUP98-X cases (0.9%) with 13 different fusion partners. Fusion partners defined disease characteristics and biology; patients with NUP98-NSD1 or NUP98-KDM5A had distinct immunophenotypic, transcriptomic, and epigenomic profiles. Unlike the two most prevalent NUP98 fusions, NUP98-X variants are typically not cryptic. Furthermore, NUP98-X cases are associated with WT1 mutations, and have epigenomic profiles that resemble either NUP98-NSD1 or NUP98-KDM5A. Cooperating FLT3-ITD and WT1 mutations define NUP98-NSD1, and chromosome 13 aberrations are highly enriched in NUP98-KDM5A. Importantly, we demonstrate that NUP98 fusions portend dismal overall survival, with the noteworthy exception of patients bearing abnormal chromosome 13 (clinicaltrials gov. Identifiers: NCT00002798, NCT00070174, NCT00372593, NCT01371981).</p

Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Contact with HIV-1 envelope protein elicits release of ATP through pannexin-1 channels on target cells; by activating purinergic receptors and Pyk2 kinase in target cells, this extracellular ATP boosts HIV-1 infectivity